In order to study the effect of ethanol and other drugs on folate metabolism, a quantitative assay for hepatic conversion of folic acid to N-5-methyltetrahydrofolic acid (MTHF) will be perfected in normal subjects. This assay will involve an intravenous injection of tritiated folic acid followed by an intravenous flushing dose of unlabeled folic acid, with separation of tritiated folic acid from tritiated MTHF by anion exchange column chromatography of plasma and urine. In this way, a normal ratio for hepatic conversion of folic acid to MTHF will be established. Normal volunteers will then be studied on oral ethanol regimens and control regimens. The ratio of conversion of folic acid to MTHF for the ethanol study of each subject will be compared to the control ratio for that subject and to the established normal ratio. In another protocol, the effect of oral ethanol on urinary excretion of folate metabolites will be investigated. It is anticipated that these studies will show that ethanol does not enhance urinary folate loss and will establish whether or not ethanol impairs conversion of folic acid to MTHF. The effect of short-term ingestion of diphenylhydantoin on the serum folate level as determined by the L. casei assay and the radioassay will also be investigated. If diphenylhydantoin is shown to lower the serum folate level, the causal mechanism will be sought by the prcedures described above for the study of the effect of ethanol on folate metabolism. Finally, the frequency, degree, and hematologic consequences of folate deficiency in women taking oral contraceptives will be explored. It is hoped that the mechanisms by which ethanol and diphenylhydantoin impair folate metabolism will be established, and that the knowledge gained about folate metabolism will benefit many fields of scientific endeavor.